Histotripsy and Lithotripsy are non-invasive tissue ablation modalities that focus pulsed ultrasound from outside the body to a target tissue inside the body. Histotripsy mechanically damages tissue through cavitation of microbubbles, and Lithotripsy is typically used to fragment urinary stones with acoustic shockwaves.
Histotripsy is the mechanical disruption via acoustic cavitation of a target tissue volume or tissue embedded inclusion as part of a surgical or other therapeutic procedure. Histotripsy works best when a whole set of acoustic and transducer scan parameters controlling the spatial extent of periodic cavitation events are within a rather narrow range. Small changes in any of the parameters can result in discontinuation of the ongoing process.
Histotripsy requires high peak intensity acoustic pulses which in turn require large surface area focused transducers. These transducers are often very similar to the transducers used for Lithotripsy and often operate in the same frequency range. The primary difference is in how the devices are driven electrically.
As shown by FIGS. 1A-1B, Histotripsy pulses comprise (usually) small number of cycles of a sinusoidal driving voltage whereas Lithotripsy is (most usually) driven by a single high voltage pulse with the transducer responding at its natural frequencies. Even though the Lithotripsy pulse is only one cycle, its negative pressure phase length is equal to or greater than the entire length of the Histotripsy pulse, lasting tens of microseconds. This negative pressure phase allows generation and continual growth of the bubbles, resulting in bubbles of sizes up to 1 mm. The Lithotripsy pulses use the mechanical stress produced by a shockwave and these 1 mm bubbles to fracture the stones into smaller pieces.
In comparison, each negative and positive cycle of a Histotripsy pulse grows and collapses the bubbles, and the next cycle repeats the same process. The maximal sizes of bubbles reach approximately tens to hundreds of microns. These micron size bubbles interact with a tissue surface to mechanically damage tissue.
In addition, Histotripsy delivers hundreds to thousands of pulses per second, i.e., 100-1 kHz pulse repetition frequency. Lithotripsy only works well within a narrow range of pulse repetition frequency (usually 0.5-2 Hz, which is the current limit in the United States and in Europe, however higher limits up to 4-5 Hz are contemplated). Studies show that the efficacy and efficiency of Lithotripsy decreases significantly when the pulse repetition frequency is increased to 10-100 Hz. The reduced efficiency is likely due to the increased number of mm size bubbles blocking the shock waves and other energy from reaching the stone.
Prior art treatment of nephrolithiasis (urinary stones) included early generation hydroelectric spark gap Lithotripters, such as the Donier HM3, which targeted a large treatment area, covering a sizeable portion of the kidney. For this reason, treatment success rates were high without the need for precise image guidance, yet substantial damage to the kidney tissue within the large focal volume also occurred. Subsequent Lithotripter development was focused on reducing renal injury by decreasing the focal volume. Some of the current third generation Lithotripters use piezoelectric (PZT) transducers, such as the Richard Wolf Piezolith 3000. The PZT transducer focused ultrasound in a small treatment region. Fluoroscope and ultrasound imaging can be utilized to target the urinary stones prior to and during treatment. By virtue of the smaller focus, the newer generation Lithotripters have reduced collateral tissue damage, but at the expense of success rates. Inaccuracies of targeting and respiratory motion of the kidneys decrease the fraction of pulses that directly impact the targeted stone.
Histotripsy also uses focused PZT transducers but has a different driving system. It uses ultrasound imaging to target the focused ultrasound to the stone and monitor the treatment in real time. The bubble clouds generated by Histotripsy show as a temporally changing hyperechoic zone on ultrasound images. The real-time guidance makes it possible to track the stone movement and adjust the focus position, thus further reducing possible collateral tissue damage. As described earlier, stone fragments produced by lithotripter vary from small granules less than 1.0 mm diameter to macroscopic fragments with diameters significantly greater than 1 mm (as shown in FIG. 2A), while Histotripsy erodes stones into fine particles smaller than 100 μm (as shown in FIG. 2B). Table 1 lists the Histotripsy and Lithotripsy parameters for comparison.
TABLE 1Histotripsy and Lithotripsy ParametersParametersHistotripsyLithotripsyEnergy SourceShort ultrasoundShort ultrasoundpulsespulsesImage GuidanceUltrasoundFluoroscopy,UltrasoundPeak negative pressure~8-40MPa~10-25MPaPeak positive pressure~30-200MPa~50-200MPaPulse Length3-20cycles1cycleDuty Cycle≦5%<0.1%Pulse Repetition Frequency≦5kHz≦2Hz
Shockwave Lithotripsy is favorable in that it is a short (˜30 minute) outpatient procedure that requires only IV sedation in the vast majority of patients. Post-operative pain generally resolves within 1-2 days. Ureteroscopy and percutaneous nephrolithotomy generally require general anesthesia. Although ureteroscopy is an outpatient procedure, patients often suffer with pain and discomfort from a ureteral stent for 4-7 days after treatment. Disadvantages of Lithotripsy include a stone free rate of ˜65% percent 4 weeks after treatment (compared with 90-95% stone free rate in patients having percutaneous and ureteroscopic procedures) and the necessity and occasionally discomfort of passing stone fragments following treatment. Furthermore, urinary stones fragmented using shockwave Lithotripsy can remain up to several mm in size and include sharp or jagged edges that make them difficult and painful to pass through the urinary tract.